| Stability of mitochondrial DNA against reactive oxygen species (ROS) generated in diabetes. | |
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MedLine Citation:
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PMID: 21484980 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: Increased production of ROS in mitochondria has been proposed as pathogenic mechanism for chronic complications of diabetes. Mitochondrial DNA (mtDNA) is more vulnerable to ROS. However, there are few data on the mtDNA damage in diabetes only from patients with different duration of the disease and tissues not relevant for the chronic complications of diabetes. We therefore proposed to study the stability of the mtDNA in controlled experimental conditions, in order to understand its contribution for chronic complications of diabetes. METHODS: The mtDNA damage was evaluated by long fragment polymerase chain reaction (LPCR) in human dermal fibroblasts (HDF) exposed to high glucose and hypoxia (as additional source of ROS) or in organs from diabetic animals (db/db mice) at different ages. ROS production was assessed in vitro by fluorescence and in vivo by nitrosylation of the proteins. The antioxidant enzymes were assessed by enzyme activity and by qRT-PCR and the mitochondrial repairing activity (BER) by using abasic site-containing oligonucleotides as substrates. RESULTS: Hyperglycemia when combined with hypoxia is able to induce mtDNA damage in HDF. The deleterious effect is mediated by mitochondrial ROS, being abolished when the mitochondria electron transport is blocked. The accumulation of mtDNA damage in vivo is however decreased in "old" diabetic animals (db/db) despite higher ROS levels. This mtDNA protection might be conferred by an increased BER activity. CONCLUSION: Increased BER activity in tissues affected by chronic complications of diabetes is a potential mechanism that can overcome mtDNA damage induced by hyperglycemia-related ROS overproduction. Copyright © 2011 John Wiley & Sons, Ltd. |
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Authors:
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Octavian Savu; Vivekananda Gupta Sunkari; Ileana Ruxandra Botusan; Jacob Grünler; Andrej Nikolsjkov; Sergiu-Bogdan Catrina |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-12 |
Journal Detail:
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Title: Diabetes/metabolism research and reviews Volume: - ISSN: 1520-7560 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100883450 Medline TA: Diabetes Metab Res Rev Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 John Wiley & Sons, Ltd. |
Affiliation:
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Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; National Institute for Diabetes "N.C. Paulescu", Bucharest, Romania. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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